Abstract
Amylin and adrenomedullin, members of the calcitonin peptide family, are anabolic to bone. Here, we report overlapping molecular mechanisms by which amylin, adrenomedullin, and IGF-1 induce osteoblast proliferation. Co-treatment of osteoblastic cells with amylin or adrenomedullin and IGF-1 failed to induce an additive mitogenic effect. In osteoblastic cells, neutralization of the IGF-1 receptor blocked the proliferative effects of amylin and adrenomedullin, while neutralization of IGF-1 did not. Neither amylin- nor adrenomedullin-induced mitogenic signaling or cell proliferation in IGF-1 receptor-null fibroblasts. In addition, amylin and adrenomedullin receptor blockers inhibited the proliferative effects of IGF-1 in osteoblastic cells. These findings demonstrate overlap in the molecular mechanisms by which amylin, adrenomedullin, and IGF-1 induce mitogenesis in osteoblasts, and an important role for the IGF-1 receptor in the mitogenic actions of amylin and adrenomedullin. Our findings are potentially important in refining these peptides for the therapy of osteoporosis.
MeSH terms
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Adrenomedullin
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Amyloid / metabolism
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Amyloid / pharmacology*
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Animals
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Cell Division / drug effects
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Cells, Cultured
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Enzyme Activation / drug effects
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Fibroblasts / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Humans
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Insulin-Like Growth Factor I / antagonists & inhibitors
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Insulin-Like Growth Factor I / pharmacology*
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Islet Amyloid Polypeptide
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Mitogens / pharmacology*
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Osteoblasts / cytology*
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Osteoblasts / drug effects*
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Peptides / metabolism
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Peptides / pharmacology*
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Rats
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Receptor, IGF Type 1 / metabolism
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Receptors, Islet Amyloid Polypeptide
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Receptors, Peptide / antagonists & inhibitors
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Signal Transduction
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Transforming Growth Factor beta / pharmacology
Substances
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Amyloid
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Islet Amyloid Polypeptide
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Mitogens
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Peptides
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Receptors, Islet Amyloid Polypeptide
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Receptors, Peptide
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Transforming Growth Factor beta
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Adrenomedullin
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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GTP-Binding Protein alpha Subunits, Gi-Go